Variations in the four and a half LIM domains 1 gene (FHL1) are associated with fasting insulin and insulin sensitivity responses to regular exercise

M. Teran-Garcia, T. Rankinen, T. Rice, A. S. Leon, D. C. Rao, J. S. Skinner, C. Bouchard

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Aims/hypothesis: The expression of the four and a half LIM domains 1 gene (FHL1) is increased in the muscle of individuals who show an improvement in insulin sensitivity index (S I) after 20 weeks of exercise training. The aim of the present study was to investigate associations between three FHL1 single nucleotide polymorphisms (SNPs) and variables derived from an IVGTT, both in the sedentary state and in response to exercise training, in participants in the HERITAGE Family Study. Materials and methods: SNPs were typed using fluorescence polarisation methodology. Analyses were performed separately by sex and in black and white individuals. Results: In black participants, no associations were found with any of the SNPs. In white women (n = 207), SNP rs9018 was associated with the disposition index (D I), which is calculated as S I generated from the MINMOD program (×10 -4 min-1[μU/ml]-1) multiplied by acute insulin response to glucose (AIRg; pmol/l × 10 min), and the glucose disappearance index (K g) training responses (p = 0.016 and p = 0.008, respectively). In white men (n = 222), all SNPs were associated with fasting glucose levels (p ≤ 0.05) and SNP rs2180062 with the insulin sensitivity index (S I) (p = 0.04) in the sedentary state. Two SNPs were associated with fasting insulin training response. Fasting insulin decreased to a greater extent in carriers of the rs2180062 C allele (p = 0.01) and rs9018 T allele (p = 0.04). With exercise training, S I (×10-4 min-1[μU/ml]-1: 0.68 ± 0.20 vs -0.77 ± 0.44, p = 0.046), D I (319 ± 123 vs -528 ± 260, p = 0.006) and K g (per 100 min: 0.09 ± 0.04 vs -0.14 ± 0.8, p = 0.03) improved more in the C allele carriers at rs2180062 than in the T allele carriers. Conclusions/interpretation: Fasting insulin and S I responses to exercise training were associated with DNA sequence variation in FHL1 in white men. Whether these associations exist only in white men remains to be investigated.

Original languageEnglish (US)
Pages (from-to)1858-1866
Number of pages9
Issue number9
StatePublished - Sep 2007

Bibliographical note

Funding Information:
Acknowledgements The HERITAGE Family Study is supported by the National Heart, Lung, and Blood Institute Grants HL-45670 (C. Bouchard), HL-47323 (A. S. Leon), HL-47317 (D. C. Rao) and HL-47327 (J. S. Skinner). A. S. Leon is partially supported by the Henry L. Taylor endowed Professorship in Exercise Science and Health Enhancement and C. Bouchard is partially supported by the George A. Bray Chair in Nutrition. We thank J. H. Wilmore for his contribution to this study. We thank N. Laidlaw for editorial support.


  • FHL1
  • Gene-exercise interaction
  • KYO-T
  • Polymorphism
  • Risk factors
  • SLIM1
  • SNP
  • Single nucleotide polymorphism


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